HLA-B27, axial spondyloarthritis and survival.

Introduction: Ankylosing spondylitis (AS), and carriage of gene in otherwise healthy individuals, are reportedly associated with increased mortality. We evaluated this hypothesis, using data from both a 35-year AS follow-up study and UK Biobank data.

Methods: In 1985, 363 members of the Swiss AS Patient Society and 806 relatives were screened clinically and then radiographically for AS/axial spondyloarthritis (axSpA).

Correction: Stoll et al. Impact of HLA-B27 and Disease Status on the Gut Microbiome of the Offspring of Ankylosing Spondylitis Patients. 2022, , 569.

The authors wish to make the following correction to this paper [...

Recurrence of axial spondyloarthritis among first-degree relatives in a prospective 35-year-follow-up family study.

Objective: The lifetime recurrence rate (RR) of axial spondyloarthritis (axSpA) among first-degree relatives (FDR) and the effect of proband's gender, HLA-B27 and radiographic status is unclear. Our 35-year-follow-up family study has enabled these issues to be addressed.

Methods: In 1985, 363 ankylosing spondylitis (AS) probands (members of the Swiss AS Patient Society) and 806 FDR recruited into the study, completed questionnaires regarding axSpA manifestations, underwent a physical examination and most also underwent pelvic radiography and HLA-B27 typing.

Heterogeneity of axial spondyloarthritis: genetics, sex and structural damage matter.

Objective: Axial spondyloarthritis (axSpA) comprises both radiographic and non-radiographic disease. However, the paucity of specific objective measures for the disease and current classification criteria showing suboptimal specificity contribute to disease heterogeneity observed in clinical practice and research. We used a historical cohort of patients with axSpA to assess sources of heterogeneity.

Impact of HLA-B27 and Disease Status on the Gut Microbiome of the Offspring of Ankylosing Spondylitis Patients.

Multiple studies have shown the microbiota to be abnormal in patients with spondyloarthritis (SpA). The purpose of this study was to explore the genetic contributions of these microbiota abnormalities. We analyzed the impact of HLA-B27 on the microbiota of children at risk for SpA and compared the microbiota of HLA-B27+ pediatric offspring of ankylosing spondylitis (AS) patients with that of HLA-B27+ children with SpA.

Novel approach by natural language processing for COVID-19 knowledge discovery.

Background: The impact of COVID-19 on public health has mandated an 'all hands on deck' scientific response. The current clinical study and basic research on COVID-19 are mainly based on existing publications or our knowledge of coronavirus. However, efficiently retrieval of accurate, relevant knowledge on COVID-19 can pose significant challenges for researchers.

Factors predicting axial spondyloarthritis among first-degree relatives of probands with ankylosing spondylitis: a family study spanning 35 years.

Objective: Factors predicting axial spondyloarthritis (axSpA) among first-degree relatives (FDRs) of ankylosing spondylitis (AS) patients need to be defined. We investigated the predictive value of the probands' HLA-B27 and radiographic sacroiliitis status on disease occurrence among their FDR. We also assessed the predictive value of features of the clinical history, including chronic inflammatory back pain (CIBP) and acute anterior uveitis (AAU), among the FDR and how they can be used to improve classification and diagnosis of axSpA.

Oligofructose-Enriched Inulin Intake, Gut Microbiome Characteristics, and the V̇O2 Peak Response to High-Intensity Interval Training in Healthy Inactive Adults.

Background: The gut microbiome has been associated with cardiorespiratory fitness.

Objectives: To assess the effects of oligofructose (FOS)-enriched inulin supplementation on the gut microbiome and the peak oxygen uptake (V̇O2peak) response to high-intensity interval training (HIIT).

Methods: The study was a randomized controlled trial.

Intratumoral T-cell receptor repertoire is predictive of interim PET scan results in patients with diffuse large B-cell lymphoma treated with rituximab/cyclophosphamide/doxorubicin/prednisolone/vincristine (R-CHOP) chemoimmunotherapy.

Objectives: A diverse intratumoral T-cell receptor (TCR) repertoire is associated with improved survival in diffuse large B-cell lymphoma (DLBCL) treated with rituximab/cyclophosphamide/doxorubicin/prednisolone/vincristine (R-CHOP) chemoimmunotherapy. We explored the impact of intratumoral TCR repertoire on interim PET (iPET) done after four cycles of R-CHOP, the relationships between intratumoral and circulating repertoire, and the phenotypes of expanded clonotypes.

Methods: We sequenced the third complementarity-determining region of TCRβ in tumor samples, blood at pre-therapy and after four cycles of R-CHOP in 35 patients enrolled in ALLGNHL21 trial in high-risk DLBCL.

De novo protein design by an energy function based on series expansion in distance and orientation dependence.

Motivation: Despite many successes, de novo protein design is not yet a solved problem as its success rate remains low. The low success rate is largely because we do not yet have an accurate energy function for describing the solvent-mediated interaction between amino acid residues in a protein chain. Previous studies showed that an energy function based on series expansions with its parameters optimized for side-chain and loop conformations can lead to one of the most accurate methods for side chain (OSCAR) and loop prediction (LEAP).

Polygenic Risk Scores have high diagnostic capacity in ankylosing spondylitis.

Objective: We sought to test the hypothesis that Polygenic Risk Scores (PRSs) have strong capacity to discriminate cases of ankylosing spondylitis (AS) from healthy controls and individuals in the community with chronic back pain.

Methods: PRSs were developed and validated in individuals of European and East Asian ethnicity, using data from genome-wide association studies in 15 585 AS cases and 20 452 controls. The discriminatory values of PRSs in these populations were compared with other widely used diagnostic tests, including C-reactive protein (CRP), and sacroiliac MRI.

Genome wide association study of response to interval and continuous exercise training: the Predict-HIIT study.

Background: Low cardiorespiratory fitness (V̇O) is highly associated with chronic disease and mortality from all causes. Whilst exercise training is recommended in health guidelines to improve V̇O, there is considerable inter-individual variability in the V̇O response to the same dose of exercise. Understanding how genetic factors contribute to V̇O training response may improve personalisation of exercise programs.

Genetics and the axial spondyloarthritis spectrum.

The axial SpAs (axSpAs) are clearly clinically a heterogeneous set of diseases with markedly varying extra-articular features. These diseases are all highly heritable and have overlapping but differing genetic origins. Shared features include association with HLA class I alleles and genes of the IL-23 pathway, among other things.

Biomarker development for axial spondyloarthritis.

The term axial spondyloarthritis (axSpA) encompasses a heterogeneous group of diseases that have variable presentations, extra-articular manifestations and clinical outcomes, and that will respond differently to treatments. The prototypical type of axSpA, ankylosing spondylitis, is thought to be caused by interaction between the genetically primed host immune system and gut microbiota. Currently used biomarkers such as HLA-B27 status, C-reactive protein and erythrocyte sedimentation rate have, at best, moderate diagnostic and predictive value.

A missense mutation in the MLKL brace region promotes lethal neonatal inflammation and hematopoietic dysfunction.

MLKL is the essential effector of necroptosis, a form of programmed lytic cell death. We have isolated a mouse strain with a single missense mutation, Mlkl, that alters the two-helix 'brace' that connects the killer four-helix bundle and regulatory pseudokinase domains. This confers constitutive, RIPK3 independent killing activity to MLKL.

MHC associations of ankylosing spondylitis in East Asians are complex and involve non-HLA-B27 HLA contributions.

Background: The association of HLA-B*27 with AS is amongst the strongest of any known association of a common variant with any human disease. Nonetheless, there is strong evidence indicating that other HLA-B alleles are involved in the disease. European ethnicity studies have demonstrated risk associations with HLA-B*40 and multiple other HLA-B, HLA-A, and HLA class II alleles, and demonstrated that in that ethnic group, the amino acid sequence at position 97 in HLA-B is the key determinant of HLA associations with AS.

Hippocampal plasticity underpins long-term cognitive gains from resistance exercise in MCI.

Dementia affects 47 million individuals worldwide, and assuming the status quo is projected to rise to 150 million by 2050. Prevention of age-related cognitive impairment in older persons with lifestyle interventions continues to garner evidence but whether this can combat underlying neurodegeneration is unknown. The Study of Mental Activity and Resistance Training (SMART) trial has previously reported within-training findings; the aim of this study was to investigate the long-term neurostructural and cognitive impact of resistance exercise in Mild Cognitive Impairment (MCI).

HLA Alleles Associated With Risk of Ankylosing Spondylitis and Rheumatoid Arthritis Influence the Gut Microbiome.

Objective: HLA alleles affect susceptibility to more than 100 diseases, but the mechanisms that account for these genotype-disease associations are largely unknown. HLA alleles strongly influence predisposition to ankylosing spondylitis (AS) and rheumatoid arthritis (RA). Both AS and RA patients have discrete intestinal and fecal microbiome signatures.

Genome-wide association study in Turkish and Iranian populations identify rare familial Mediterranean fever gene (MEFV) polymorphisms associated with ankylosing spondylitis.

Ankylosing spondylitis (AS) is a highly heritable immune-mediated arthritis common in Turkish and Iranian populations. Familial Mediterranean Fever (FMF) is an autosomal recessive autoinflammatory disease most common in people of Mediterranean origin. MEFV, an FMF-associated gene, is also a candidate gene for AS.